1. Field of the Invention
The present invention concerns a fractionating apparatus for eluting samples from a plurality of columns simultaneously and dropping ingredients thereof successively each by a required amount to fractionation vessels in each of rows arranged in a matrix.
2. Statement of the Related Art
When a novel compound is prepared by combining several substances, a combinatorial chemistry has been adopted recently. In this method, several kinds of materials provided previously are mixed at different mixing ratios on every vial tubes to cause chemical reactions and synthesized a number of synthesized samples simultaneously.
A fractionating apparatus is used for purifying the thus synthesized samples and analyzing ingredients contained therein and fractionating only the optional effective ingredients.
The fractionating apparatus is adapted to fractionate the ingredients of a sample by injecting a sample to a column filled with an adsorbent such as silica, supplying a solvent from one end of the column and eluting the ingredients of the sample from the other end, depending on the difference in the elution time between each of the ingredients.
However, since several tens kinds of samples are synthesized simultaneously in the combinatorial chemistry, if fractionation is conducted on every samples, it takes as much as 6 to 7 hours for only fractionating samples even of ten kinds of them if column exchange time or the like is taken into consideration.
In view of the above, it has recently been proposed a fractionating apparatus comprising a plurality of sample elution systems in which a plurality of columns (10 to 16) are set simultaneously, a solvent is supplied at the same time to each of the columns and sample ingredients are eluted simultaneously.
According to this apparatus, since sample ingredients from the respective columns can be fractionated simultaneously by successively dropping samples eluted from each of sample elution systems in a time sequential manner into fractionation vessels in each of the rows arranged in a matrix, fractionation time can be shortened and column exchanging labor and time can also be saved.
However, since elution time is different due to the difference of the ingredients contained in each of the samples, it may sometimes occur that while sample ingredients are eluted from one column, sample ingredients are not yet eluted from other columns.
Further, the number of sample ingredients to be fractionated is different between a sample containing a large number of ingredients and a sample at a relatively high impurity with less number of ingredients.
That is, when a large number of ingredients are contained, it is necessary to reliably fractionate each of the ingredients by decreasing the amount of a solvent to be dropped to one fractionation vessel. An extremely large number of ingredients can not sometimes be coped with fractionation vessels only for one row but increase of the number of fractionation vessels in each row makes the size of the fractionating apparatus larger.
On the other hand, for a compound at a relatively high purity, it may suffice to fractionate only the portion at a high concentration of the ingredient when it is eluted, and it is not necessary to fractionate other portion at an extremely low concentration in which the aimed ingredient is not eluted.
As described above, when plurality of sample elution systems are merely provided irrespective of the difference for the timing of dropping ingredients or the amount of dropping to individual fractionation vessels in accordance with samples, eluates are dropped evenly from all of the sample elution systems into fractionation vessels, to result in a problem that the substances can not be fractionated in accordance with the ingredients contained in each of the samples.
In view of the above, it is a technical subject of this invention to enable each of the ingredients to be dropped at an optional timing on each of the sample elution systems to the fractionation vessels in each of rows in a case of providing a plurality of sample elution systems. It is a second subject of this invention to enable reliable fractionation to the last without enlarging the size of the fractionating apparatus in a case where the number of ingredients is large and can not be coped with the fractionation vessels only for one row.
For overcoming the subjects described above, this invention provides a fractionating apparatus having a required number of sample elution systems adapted to elute samples adsorbed on columns and successively drop the sample ingredients contained therein into fractionation vessels arranged in a matrix, in which each of the sample elution systems comprises a nozzle for dropping eluted sample ingredients into fractionation vessels, a drain for discharging unnecessary solvent, a valve for switching the nozzle and the drain and a driving mechanism for reciprocating each of the nozzles independently of each other along the direction of the row of the fractionation vessels, and a photosensor is disposed to the upstream of the valve for detecting the presence or absence of the sample ingredients contained in the solvent flowing in the sample elution systems and a control device is disposed for successively stopping each of the nozzles at a location just above the fractionation vessel by each of the driving mechanisms and opening the valves while a sample ingredient to be fractionated is being eluted, on the basis of the detection signal from the photosensor and the flow rate of the solvent.
According to this invention, since each of the nozzles is moved along fractionation vessels in each row by each of the driving mechanism, stopped just above an empty vessel and kept standing-by until elution of the sample ingredient is detected by the photosensor disposed to each of the sample elution systems, during which the solvent discharged from the columns is discarded to the drain.
When the elution of the sample ingredient is detected, the valve corresponding to the sample elution system is operated and the ingredient is dropped by the dropping nozzle from the fractionation vessel and the ingredient is fractionated.
Then, when the eluate is eluted by a required amount, the nozzle is moved to the next fractionation vessel and drops other sample ingredient again.
As described above, the nozzle is moved successively when the detection signal is outputted from the photosensor and the ingredient is dropped each by required amount and the ingredients are dropped successively to the fractionation vessels arranged in the direction of the row. Thus, a larger number of fractionation vessels are used when the number of ingredients is large since the output frequency for the detection signals is high, whereas a less number of fractionation vessels are used when the number of ingredients is small. Since the nozzle and the valve are operated individually on every sample elution systems, ingredients can be dropped at different timings respectively.
Since the valve is operated based on the detection signals of each of the photosensors in each of the sample elution systems, when only the solvent is discharged with no elution of the ingredients, it is discharged into a drain as it is and only when the ingredient is eluted, the ingredient can be dropped into the fractionation vessel, so that wasteful collection only for the solvent to the fractionation vessel can be avoided.
In a preferred embodiment, according to this invention, nozzles which are opened or made conductive selectively by the valve are disposed each by two on each of the sample elution systems and each of the nozzles is reciprocated together over the adjacent rows of the fractionation vessels arranged in a matrix and in the direction of the row by the driving mechanisms.
According to this preferred embodiment, when sample ingredients are fractionated, they are successively dropped from the nozzle on one side into the fractionation vessels in one row during forwarding stroke while they are dropped successively from the nozzle on the other side to the fractionation vessels in the other row during backwarding stroke, by which ingredients are fractionated divisionally into fractionation vessels in two rows, and this can cope with a case requiring a large number of fractionation vessels.
In this case, it is not necessary to move the nozzles in the lateral direction but they only have to be moved reciprocally, the structure of the nozzle driving mechanism can be made simple to reduce the worry of failure.
Further, while the number of the fractionation vessels increases in the lateral direction, since the nozzles are made reciprocatable individually in the direction of the row, the width of the driving mechanism is about twice the diameter of the fractionation vessels, so that the lateral size changes scarcely even when the number of fractionation vessels is increased by one row between the rows.